Cell Reports (May 2017)

Thymidine Catabolism as a Metabolic Strategy for Cancer Survival

  • Sho Tabata,
  • Masatatsu Yamamoto,
  • Hisatsugu Goto,
  • Akiyoshi Hirayama,
  • Maki Ohishi,
  • Takuya Kuramoto,
  • Atsushi Mitsuhashi,
  • Ryuji Ikeda,
  • Misako Haraguchi,
  • Kohichi Kawahara,
  • Yoshinari Shinsato,
  • Kentaro Minami,
  • Atsuro Saijo,
  • Masaki Hanibuchi,
  • Yasuhiko Nishioka,
  • Saburo Sone,
  • Hiroyasu Esumi,
  • Masaru Tomita,
  • Tomoyoshi Soga,
  • Tatsuhiko Furukawa,
  • Shin-ichi Akiyama

DOI
https://doi.org/10.1016/j.celrep.2017.04.061
Journal volume & issue
Vol. 19, no. 7
pp. 1313 – 1321

Abstract

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Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites were required for the survival of cells under low-glucose conditions. Furthermore, activation of thymidine catabolism was observed in human gastric cancer. These findings demonstrate that thymidine can serve as a glycolytic pathway substrate in human cancer cells.

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